The present invention is directed to an apparatus and system for preventing hypotension during aggressive diuretic therapy.
Heart failure is a common cause of hospitalization among Medicare beneficiaries and is associated with significant morbidity and mortality. Most patients hospitalized with heart failure have symptoms of congestion due to excess fluid retention. CHF (chronic heart failure) is a salt-avid state, where salt (Na) retention is based on an activation of the circulating RAAS (renin-angiotensin-aldosterone system) with consequent expansion of intravascular and extravascular volume resulting in the signs and symptoms of CHF. Loop diuretics which often are successful in generating a rapid diuresis and mild natriuresis and have become the basis of treatment of congestion. Loop diuretics have become the primary treatment for fluid overload in patients with heart failure and are used in 88% of patients hospitalized for heart failure.
Concerns about the safety of diuretic based treatment strategies for congestive heart failure have been raised. (Weber et al Am Coll Cardiol. 2004 Sep. 15;44(6):1301-7., Domanski et al Am Coll Cardiol. 2003 Aug. 20;42(4):705-8, Cooper et al Circulation. 1999 Sep. 21;100(12):1311-5, Neuberg et al Am Heart J. 2002 Ju1;144(1):31-8, Francis et al Circulation. 1990 Nov;82(5):1724-9, Emerman C, et al. Heart Failure Society of America 2004 Annual Scientific Meeting; Sep. 12-15, 2004; Toronto, ON.). Deleterious hemodynamic effects of aggressive loop diuretic strategies have long been appreciated, including acute decreases of cardiac output, increases in pulmonary capillary wedge pressure and total systemic vascular resistance have been documented (Francis AIM 1985;103:1-6). Aggressive diuretic treatment strategies are associated with decreasing renal function, as documented by reductions of both renal blood flow and glomerular filtration rates. (Gottlieb SS et al. Circulation. 2002;105:1348-1353). This deleterious effect of acute diuretic administration may be the proximate cause of worsening renal function observed in the setting of diuretic therapy. An increase of Serum Creatinine (sCr) of >0.3 mg/dl, occurs in nearly ⅓ of hospitalized heart failure patients [Butler AHJ 2004]. Progressive azotemia in this setting is associated with increase length of stay in the hospital and worse prognosis. [Butler AHJ 2004, Weinfeld AHJ 1999].
Activation of the neurohormonal system consequent to diuretic administration is associated with the observed reductions of cardiac and renal function. (Bayliss Br Heart J, 1987; 57:17-22). In addition to the renin-angiotensin-aldosterone activation associated with diuretic use, the direct renal loss of cations Ca and Mg following loop diuretics, result in stimulation of PTH release; this has been hypothesized to be linked to the long term morbidity and mortality associated with diuretic reliance in treatment strategies for CHF.(K Weber, et al). The ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult,© 2001 by the American College of Cardiology and the American Heart Association, Inc. state that the “Appropriate use of diuretics is a key element in the success of other drugs used for the treatment of HF. The use of inappropriately low doses of diuretics will cause fluid retention, which can diminish the response to ACE inhibitors and increase the risk of treatment with beta-blockers. Conversely, the use of inappropriately high doses of diuretics will lead to volume contraction, which can increase the risk of hypotension with ACE inhibitors and vasodilators and the risk of renal insufficiency with ACE inhibitors and angiotensin II receptor antagonists. Optimal use of diuretics is the cornerstone of any successful approach to the treatment of HF.”.
Beyond the concerns about the safety of loop diuretic based congestion strategies, the therapeutic efficacy of this strategy is questionable, nearly half of patients hospitalized for heart failure have less than 5 pounds of weight loss at the time of discharge [ADHERE] thus, the current treatment strategies, principally using diuretics to treat congestion related to heart failure, are largely ineffective in weight reduction. Diuretic resistance, defined as relative or absolute loss of diuresis following administration of potent loop diuretics is common. Moreover, the braking phenomenon, reduced efficacy of Na removal with each loop diuretic dose, results in attenuated efficacy of sodium removal when treatment strategies are based on loop diuretics.
Diuretic dosage is limited by the open loop nature of the drug delivery process so clinicians have to be aware of the potential for hypotension resulting in poor renal perfusion, an increase in GFR, activation of the RAAS system and the resultant poor perfusion of the kidney. It is believed that many of the deleterious effects of diuretics stem from aggressive volume depletion and that the viscous cycle can be overcome if this volume depletion is prevented. When a diuretic is administered fluid is recruited directly from the vascular volume via the kidney and if this rate exceeds the rate that the resultant oncotic pressure can recruit fluid from the interstitial space the volume in the vascular space is depleted. This replenishment rate is known as the PRR (Plasma Refill Rate). Once the diuretic is delivered to the patient, clinicians have no way to titrate its effect, thus in the event that hypotension ensues, a isotonic solution is administered to the patient intravenously to replenish the vascular volume and the patients is left to stabilize before continuing therapy. This is the current mode of practice, because no better alternative have been found. Much of the literature talks about ways of optimizing diuretic dosage accounting for the pharmakinetics of the drug and monitoring output. In clinical practice this translates to a doubling of the dose protocol over given time periods based upon measured urine output.
Hypotension is the manifestation of hypovolumea or a severe fluid misbalance. Symptomatically, hypotension may be experienced by the patient first as light-headedness. To monitor patients for hypotension, non-invasive blood pressure monitors (NIBP) are commonly used during renal replacement therapy (RRT). When detected early, hypotension resulting from the excessive loss of fluid is easily reversed by giving the patient intravenous fluids.